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Sinomenine Protects against Lipopolysaccharide-Induced Acute Lung Injury in Mice via Adenosine A(2A) Receptor Signaling

Sinomenine (SIN) is a bioactive alkaloid extracted from the Chinese medicinal plant Sinomenium acutum, which is widely used in the clinical treatment of rheumatoid arthritis (RA). However, its role in acute lung injury (ALI) is unclear. In this study, we investigate the role of SIN in lipopolysaccha...

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Autores principales: Li, Jun, Zhao, Li, He, Xie, Zeng, Yi-Jun, Dai, Shuang-Shuang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3598653/
https://www.ncbi.nlm.nih.gov/pubmed/23555007
http://dx.doi.org/10.1371/journal.pone.0059257
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author Li, Jun
Zhao, Li
He, Xie
Zeng, Yi-Jun
Dai, Shuang-Shuang
author_facet Li, Jun
Zhao, Li
He, Xie
Zeng, Yi-Jun
Dai, Shuang-Shuang
author_sort Li, Jun
collection PubMed
description Sinomenine (SIN) is a bioactive alkaloid extracted from the Chinese medicinal plant Sinomenium acutum, which is widely used in the clinical treatment of rheumatoid arthritis (RA). However, its role in acute lung injury (ALI) is unclear. In this study, we investigate the role of SIN in lipopolysaccharide (LPS)-induced ALI in mice. After ALI, lung water content and histological signs of pulmonary injury were attenuated, whereas the PaO(2)/FIO(2) (P/F) ratios were elevated significantly in the mice pretreated with SIN. Additionally, SIN markedly inhibited inflammatory cytokine TNF-α and IL-1β expression levels as well as neutrophil infiltration in the lung tissues of the mice. Microarray analysis and real-time PCR showed that SIN treatment upregulated adenosine A(2A) receptor (A(2A)R) expression, and the protective effect of SIN was abolished in A(2A)R knockout mice. Further investigation in isolated mouse neutrophils confirmed the upregulation of A(2A)R by SIN and showed that A(2A)R-cAMP-PKA signaling was involved in the anti-inflammatory effect of SIN. Taken together, these findings demonstrate an A(2A)R-associated anti-inflammatory effect and the protective role of SIN in ALI, which suggests a potential novel approach to treat ALI.
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spelling pubmed-35986532013-04-02 Sinomenine Protects against Lipopolysaccharide-Induced Acute Lung Injury in Mice via Adenosine A(2A) Receptor Signaling Li, Jun Zhao, Li He, Xie Zeng, Yi-Jun Dai, Shuang-Shuang PLoS One Research Article Sinomenine (SIN) is a bioactive alkaloid extracted from the Chinese medicinal plant Sinomenium acutum, which is widely used in the clinical treatment of rheumatoid arthritis (RA). However, its role in acute lung injury (ALI) is unclear. In this study, we investigate the role of SIN in lipopolysaccharide (LPS)-induced ALI in mice. After ALI, lung water content and histological signs of pulmonary injury were attenuated, whereas the PaO(2)/FIO(2) (P/F) ratios were elevated significantly in the mice pretreated with SIN. Additionally, SIN markedly inhibited inflammatory cytokine TNF-α and IL-1β expression levels as well as neutrophil infiltration in the lung tissues of the mice. Microarray analysis and real-time PCR showed that SIN treatment upregulated adenosine A(2A) receptor (A(2A)R) expression, and the protective effect of SIN was abolished in A(2A)R knockout mice. Further investigation in isolated mouse neutrophils confirmed the upregulation of A(2A)R by SIN and showed that A(2A)R-cAMP-PKA signaling was involved in the anti-inflammatory effect of SIN. Taken together, these findings demonstrate an A(2A)R-associated anti-inflammatory effect and the protective role of SIN in ALI, which suggests a potential novel approach to treat ALI. Public Library of Science 2013-03-15 /pmc/articles/PMC3598653/ /pubmed/23555007 http://dx.doi.org/10.1371/journal.pone.0059257 Text en © 2013 Li et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Li, Jun
Zhao, Li
He, Xie
Zeng, Yi-Jun
Dai, Shuang-Shuang
Sinomenine Protects against Lipopolysaccharide-Induced Acute Lung Injury in Mice via Adenosine A(2A) Receptor Signaling
title Sinomenine Protects against Lipopolysaccharide-Induced Acute Lung Injury in Mice via Adenosine A(2A) Receptor Signaling
title_full Sinomenine Protects against Lipopolysaccharide-Induced Acute Lung Injury in Mice via Adenosine A(2A) Receptor Signaling
title_fullStr Sinomenine Protects against Lipopolysaccharide-Induced Acute Lung Injury in Mice via Adenosine A(2A) Receptor Signaling
title_full_unstemmed Sinomenine Protects against Lipopolysaccharide-Induced Acute Lung Injury in Mice via Adenosine A(2A) Receptor Signaling
title_short Sinomenine Protects against Lipopolysaccharide-Induced Acute Lung Injury in Mice via Adenosine A(2A) Receptor Signaling
title_sort sinomenine protects against lipopolysaccharide-induced acute lung injury in mice via adenosine a(2a) receptor signaling
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3598653/
https://www.ncbi.nlm.nih.gov/pubmed/23555007
http://dx.doi.org/10.1371/journal.pone.0059257
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